Cytochrome P-450 appears to catalyze the in vitro formation of phosgene (COCl2) and carbon dioxide (CO2) from chloroform (CHCl3) in rat liver microsomes, since these reactions are NADPH dependent and inhibited by carbon monoxide and SKF 525-A. Moreover, the cleavage of the C-H bond appears to be the rate determining step in this process since deuterium labeled chloroform (CDCl3) is biotransformed into COCl2 slower that CHCl3. This oxidative dehalogenation pathway is believed to have general metabolic and toxicological importance for other halocarbon drugs and environmental chemicals.